Assessing the location and performance of replacement heart valves

ABSTRACT

Methods and devices for assessing the operation of a replacement heart valve. The method includes endovascularly delivering a replacement heart valve to a vicinity of a heart valve in an unexpanded configuration, and assessing the operation of the replacement heart valve in the vicinity of the heart valve before fully expanding the replacement heart valve. Methods and devices for assessing the location of a replacement heart valve. The method includes endovascularly delivering a replacement heart valve to a vicinity of the heart valve in an unexpanded configuration, expanding the replacement heart valve to a partially deployed configuration, and assessing the location of the replacement heart valve in the vicinity of the heart valve before fully expanding the replacement heart valve.

CROSS-REFERENCE

This application is a continuation-in-part of application Ser. No. 10/746,280, filed Dec. 23, 2003, now U.S. Pat. No. 8,840,663 which is incorporated herein by reference in its entirety. This application is also a continuation-in-part of application Ser. No. 10/971,535, filed Oct. 21, 2004 now U.S. Pat. No. 8,343,213; which is a continuation-in-part of application Ser. No. 10/746,240, filed Dec. 23, 2003 now abandoned, which are incorporated herein by reference in their entirety.

BACKGROUND OF THE INVENTION

Heart valve surgery is used to repair or replace diseased heart valves. Valve surgery is an open-heart procedure conducted under general anesthesia. An incision is made through the patients's sternum (sternotomy), and the patients's heart is stopped while blood flow is rerouted through a heart-lung bypass machine.

Valve replacement may be indicated when there is a narrowing of the native heart valve, commonly referred to as stenosis, or when the native valve leaks or regurgitates. When replacing the valve, the native valve is excised and replaced with either a biologic or a mechanical valve. Mechanical valves require lifelong anticoagulant medication to prevent blood clot formation, and clicking of the valve often may be heard through the chest. Biologic tissue valves typically do not require such medication. Tissue valves may be obtained from cadavers or may be porcine or bovine, and are commonly attached to synthetic rings that are secured to the patients's heart.

Valve replacement surgery is a highly invasive operation with significant concomitant risk. Risks include bleeding, infection, stroke, heart attack, arrhythmia, renal failure, adverse reactions to the anesthesia medications, as well as sudden death. 2-5% of patients die during surgery.

Post-surgery, patients temporarily may be confused due to emboli and other factors associated with the heart-lung machine. The first 2-3 days following surgery are spent in an intensive care unit where heart functions can be closely monitored. The average hospital stay is between 1 to 2 weeks, with several more weeks to months required for complete recovery.

In recent years, advancements in minimally invasive surgery and interventional cardiology have encouraged some investigators to pursue percutaneous replacement of the aortic heart valve. Percutaneous Valve Technologies (“PVT”) of Fort Lee, N.J., has developed a balloon-expandable stent integrated with a bioprosthetic valve. The stent/valve device is deployed across the native diseased valve to permanently hold the valve open, thereby alleviating a need to excise the native valve and to position the bioprosthetic valve in place of the native valve. PVT's device is designed for delivery in a cardiac catheterization laboratory under local anesthesia using fluoroscopic guidance, thereby avoiding general anesthesia and open-heart surgery. The device was first implanted in a patient in April of 2002.

PVT's device suffers from several drawbacks. Deployment of PVT's stent is not reversible, and the stent is not retrievable. This is a critical drawback because improper positioning too far up towards the aorta risks blocking the coronary ostia of the patient. Furthermore, a misplaced stent/valve in the other direction (away from the aorta, closer to the ventricle) will impinge on the mitral apparatus and eventually wear through the leaflet as the leaflet continuously rubs against the edge of the stent/valve.

Another drawback of the PVT device is its relatively large cross-sectional delivery profile. The PVT system's stent/valve combination is mounted onto a delivery balloon, making retrograde delivery through the aorta challenging. An antegrade transseptal approach may therefore be needed, requiring puncture of the septum and routing through the mitral valve, which significantly increases complexity and risk of the procedure. Very few cardiologists are currently trained in performing a transseptal puncture, which is a challenging procedure by itself.

Other prior art replacement heart valves use self-expanding stents as anchors. In the endovascular aortic valve replacement procedure, accurate placement of aortic valves relative to coronary ostia and the mitral valve is critical. Standard self-expanding systems have very poor accuracy in deployment, however. Often the proximal end of the stent is not released from the delivery system until accurate placement is verified by fluoroscopy, and the stent typically jumps once released. It is therefore often impossible to know where the ends of the stent will be with respect to the native valve, the coronary ostia and the mitral valve.

Also, visualization of the way the new valve is functioning prior to final deployment is very desirable. Visualization prior to final and irreversible deployment cannot be done with standard self-expanding systems, however, and the replacement valve is often not fully functional before final deployment.

Another drawback of prior art self-expanding replacement heart valve systems is their lack of radial strength. In order for self-expanding systems to be easily delivered through a delivery sheath, the metal needs to flex and bend inside the delivery catheter without being plastically deformed. In arterial stents, this is not a challenge, and there are many commercial arterial stent systems that apply adequate radial force against the vessel wall and yet can collapse to a small enough of a diameter to fit inside a delivery catheter without plastically deforming. However when the stent has a valve fastened inside it, as is the case in aortic valve replacement, the anchoring of the stent to vessel walls is significantly challenged during diastole. The force to hold back arterial pressure and prevent blood from going back inside the ventricle during diastole will be directly transferred to the stent/vessel wall interface. Therefore the amount of radial force required to keep the self expanding stent/valve in contact with the vessel wall and not sliding will be much higher than in stents that do not have valves inside of them. Moreover, a self-expanding stent without sufficient radial force will end up dilating and contracting with each heartbeat, thereby distorting the valve, affecting its function and possibly migrating and dislodging completely. Simply increasing strut thickness of the self-expanding stent is not a practical solution as it runs the risk of larger profile and/or plastic deformation of the self-expanding stent.

U.S. Patent Publication No. 2002/0151970 to Garrison et al. describes a two-piece device for replacement of the aortic valve that is adapted for delivery through a patients's aorta. A stent is endovascularly placed across the native valve, then a replacement valve is positioned within the lumen of the stent. By separating the stent and the valve during delivery, a profile of the device's delivery system may be sufficiently reduced to allow aortic delivery without requiring a transseptal approach. Both the stent and a frame of the replacement valve may be balloon-expandable or self-expanding.

While providing for an aortic approach, devices described in the Garrison patent application suffer from several drawbacks. First, the stent portion of the device is delivered across the native valve as a single piece in a single step, which precludes dynamic repositioning of the stent during delivery. Stent foreshortening or migration during expansion may lead to improper alignment.

Additionally, Garrison's stent simply crushes the native valve leaflets against the heart wall and does not engage the leaflets in a manner that would provide positive registration of the device relative to the native position of the valve. This increases an immediate risk of blocking the coronary ostia, as well as a longer-term risk of migration of the device post-implantation. Further still, the stent comprises openings or gaps in which the replacement valve is seated post-delivery. Tissue may protrude through these gaps, thereby increasing a risk of improper seating of the valve within the stent.

In view of drawbacks associated with previously known techniques for endovascularly replacing a heart valve, it would be desirable to provide methods and apparatus that overcome those drawbacks.

SUMMARY OF THE INVENTION

One aspect of the invention is a method of assessing the operation of a replacement heart valve. The method comprises endovascularly delivering a replacement heart valve to a vicinity of a heart valve in an unexpanded configuration, and assessing the operation of the replacement heart valve in the vicinity of the heart valve before fully expanding the replacement heart valve.

In some embodiments of the method the replacement heart valve includes a proximal end and a distal end, and assessing the operation of the replacement heart valve includes assessing the operation of the heart valve when the proximal end of the replacement heart valve is not engaging native tissue. Delivering can include delivering the replacement heart valve within a delivery catheter, and wherein assessing the operation of the replacement heart valve comprises assessing the operation of the replacement heart valve while the proximal end of the replacement heart valve is disposed within the delivery catheter.

In some embodiments of the method assessing the operation of the replacement heart valve includes controlling blood flow through the replacement heart valve.

In some embodiments expanding the replacement heart valve to a fully expanded configuration includes expanding the replacement heart valve to a partially deployed configuration. Expanding the replacement heart valve to a partially deployed configuration can include allowing the replacement heart valve to self-expand to the partially deployed configuration. Assessing the operation of the replacement heart valve can occur after the replacement heart has self-expanded to the partially deployed configuration and before the replacement heart valve is expanded to the fully expanded configuration.

In some embodiments of the method assessing the operation of the replacement heart valve includes visually observing, such as with at least one medical imaging technique, the operation of the replacement heart valve. Assessing the operation of the replacement heart valve can include assessing the blood flow through or around the replacement heart valve. Assessing the blood flow through or around the replacement heart valve can include assessing at least one of effective orifice, ejection fraction, and regurgitation. Assessing the blood flow through or around the replacement heart valve can also include assessing at least one of valve leakage, valve positioning, and valve sizing. An injectable marker may be used during assessment of the operation of the replacement valve.

In some embodiments the method also includes assessing the function of a mitral valve.

In some embodiments the method also includes reassessing the operation of the replacement heart valve after expanding the replacement heart valve to the fully expanded configuration.

In some embodiments the method also includes repositioning the replacement heart valve after assessing the operation of the replacement heart valve, and further includes reassessing the operation of the replacement heart valve after repositioning the replacement heart valve. Repositioning the replacement heart valve can include collapsing and re-expanding the replacement heart valve.

One aspect of the invention is a method of assessing the location of a replacement heart valve. The method comprises endovascularly delivering a replacement heart valve to a vicinity of the heart valve in an unexpanded configuration, expanding the replacement heart valve to a partially deployed configuration, and assessing the location of the replacement heart valve in the vicinity of the heart valve before fully expanding the replacement heart valve.

In some embodiments expanding the replacement heart valve to a partially deployed configuration comprises controlling blood flow through the replacement heart valve, which can include allowing replacement heart valve leaflets to function.

In some embodiments expanding the replacement heart valve to the partially deployed configuration includes allowing the replacement heart valve to self-expand to the partially deployed configuration.

In some embodiments assessing the location of the replacement heart valve includes visually observing, such as with at least one medical imaging technique, the location of at least a portion of the replacement heart valve in relation to at least one native landmark. The at least one native landmark can includes at least one of a coronary ostia, native valve leaflets; calcium nodules within the leaflets or the aortic wall, a sinus, the native annulus, or the mitral valve. The at least one native landmark can include the native annulus, and the visually observing step includes visually observing the mid-section of the replacement valve in relation to the annulus. In some embodiments the at least one native landmark includes a coronary ostia, and wherein the visually observing step comprises visually observing a proximal end portion of the replacement heart valve in relation to the coronary ostia. The at least one native landmark can also include a mitral valve, and the visually observing step can include visually observing a distal end portion of the replacement heart valve in relation to the mitral valve.

In some embodiments the method further includes assessing the operation of the replacement heart valve.

In some embodiments the method further includes assessing the location after the replacement heart valve is expanded to the fully deployed configuration.

In some embodiments the method further includes repositioning the replacement valve after assessing the location, and reassessing the location after repositioning the replacement heart valve. Repositioning can include collapsing and re-expanding the replacement heart valve.

In some embodiments the method also includes locking the replacement valve in the fully deployed configuration.

Another aspect of the invention is a method of assessing the placement of a replacement heart valve. The method includes endovascularly delivering a replacement heart valve to a vicinity of the heart valve in an unexpanded configuration and assessing the location and operation of the replacement heart valve in the vicinity of the heart valve before fully deploying the replacement heart valve.

Another aspect of the invention is a method of determining the size of a replacement heart valve for a patient. The method includes measuring the change in the diameter of the aortic annulus during the cardiac cycle, measuring the patients's blood pressure, and determining the size of a replacement heart valve based on the measured diameter changes and the pressure measurements.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:

FIGS. 1A-B are elevational views of a replacement heart valve and anchor according to one embodiment of the invention.

FIGS. 2A-B are sectional views of the anchor and valve of FIGS. 1A-B.

FIGS. 3A-B show delivery and deployment of a replacement heart valve and anchor, such as the anchor and valve of FIGS. 1 and 2.

FIGS. 4A-F also show delivery and deployment of a replacement heart valve and anchor, such as the anchor and valve of FIGS. 1 and 2.

FIGS. 5A-F show the use of a replacement heart valve and anchor to replace an aortic valve.

FIGS. 6A-F show the use of a replacement heart valve and anchor with a positive registration feature to replace an aortic valve.

FIG. 7 shows the use of a replacement heart valve and anchor with an alternative positive registration feature to replace an aortic valve.

FIGS. 8A-C show another embodiment of a replacement heart valve and anchor according to the invention.

FIGS. 9A-H show delivery and deployment of the replacement heart valve and anchor of FIGS. 8A-C.

FIG. 10 is a cross-sectional drawing of the delivery system used with the method and apparatus of FIGS. 8A-C and 9A-H.

FIGS. 1A-C show alternative locks for use with replacement heart valves and anchors of this invention.

FIGS. 12A-C show a vessel wall engaging lock for use with replacement heart valves and anchors of this invention.

FIG. 13 demonstrates paravalvular leaking around a replacement heart valve and anchor.

FIG. 14 shows a seal for use with a replacement heart valve and anchor of this invention.

FIGS. 15A-E show alternative arrangements of seals on a replacement heart valve and anchor.

FIGS. 16A-C show alternative seal designs for use with replacement heart valves and anchors.

FIG. 17 shows an alternative anchor lock embodiment in an unlocked configuration.

FIG. 18 shows the anchor lock of FIG. 17 in a locked configuration.

FIG. 19 shows an alternative anchor deployment tool attachment and release mechanism for use with the invention.

FIG. 20 shows the attachment and release mechanism of FIG. 19 in the process of being released.

FIG. 21 shows the attachment and release mechanism of FIGS. 19 and 20 in a released condition.

FIG. 22 shows an alternative embodiment of a replacement heart valve and anchor and a deployment tool according to the invention in an undeployed configuration.

FIG. 23 shows the replacement heart valve and anchor of FIG. 22 in a partially deployed configuration.

FIG. 24 shows the replacement heart valve and anchor of FIGS. 22 and 23 in a more fully deployed configuration but with the deployment tool still attached.

FIG. 25 shows yet another embodiment of the delivery and deployment apparatus of the invention in use placement heart valve and anchor.

FIG. 26 shows the delivery and deployment apparatus of FIG. 25 in the process of deploying a with a replacement heart valve and anchor.

FIG. 27 show an embodiment of the invention employing seals at the interface of the replacement heart valve and anchor and the patients's tissue.

FIG. 28 is a longitudinal cross-sectional view of the seal shown in FIG. 27 in compressed form.

FIG. 29 is a transverse cross-sectional view of the seal shown in FIG. 28.

FIG. 30 is a longitudinal cross-sectional view of the seal shown in FIG. 27 in expanded form.

FIG. 31 is a transverse cross-sectional view of the seal shown in FIG. 30.

FIG. 32 shows yet another embodiment of the replacement heart valve and anchor of this invention in an undeployed configuration.

FIG. 33 shows the replacement heart valve and anchor of FIG. 32 in a deployed configuration.

FIG. 34 shows the replacement heart valve and anchor of FIGS. 32 and 33 deployed in a patients's heart

FIGS. 35A-H show yet another embodiment of a replacement heart valve, anchor and deployment system according to this invention.

FIGS. 36A-E show more detail of the anchor of the embodiment shown in FIGS. 35A-H.

FIGS. 37A-B show other embodiments of the replacement heart valve and anchor of the invention.

FIGS. 38A-C illustrate a method for endovascularly replacing a patients's diseased heart valve.

FIGS. 39A-B show an anchor for use in a two-piece replacement heart valve and anchor embodiment of the invention.

FIGS. 40A-B show a replacement heart valve for use in a two-piece replacement heart valve and anchor embodiment of the invention.

FIGS. 41A-D show a method of coupling the anchor of FIGS. 39 and the replacement heart valve of FIGS. 40.

FIG. 42 shows a delivery system for use with the apparatus shown in FIGS. 39-41.

FIG. 43 shows an alternative embodiment of a delivery system for use with the apparatus shown in FIGS. 39-41.

FIG. 44 shows yet another alternative embodiment of a delivery system for use with the apparatus shown in FIGS. 39-41.

FIGS. 45A-I illustrate a method of delivering and deploying a two-piece replacement heart valve and anchor.

FIGS. 46A-B shows another embodiment of a two-piece replacement heart valve and anchor according to this invention.

FIG. 47 shows yet another embodiment of a two-piece replacement heart valve and anchor according to this invention.

FIG. 48 shows yet another embodiment of a two-piece replacement heart valve and anchor according to this invention.

FIG. 49 shows an exemplary replacement heart valve beginning to emerge from a delivery catheter.

FIGS. 50 and 51 show a functional replacement heart valve in which the proximal end of the anchor remains disposed in the delivery catheter.

FIG. 52 shows a functional heart valve in which the proximal end of the anchor has emerged from the delivery catheter.

FIG. 53 shows an exemplary functional replacement heart valve in a partially deployed, self-expanded configuration.

DETAILED DESCRIPTION OF THE INVENTION

With reference now to FIGS. 1-4, a first embodiment of replacement heart valve apparatus in accordance with the present invention is described, including a method of actively foreshortening and expanding the apparatus from a delivery configuration and to a deployed configuration. Apparatus 10 comprises replacement valve 20 disposed within and coupled to anchor 30. FIGS. 1 schematically illustrate individual cells of anchor 30 of apparatus 10, and should be viewed as if the cylindrical anchor has been cut open and laid flat. FIGS. 2 schematically illustrate a detail portion of apparatus 10 in side-section.

Anchor 30 has a lip region 32, a skirt region 34 and a body region 36. First, second and third posts 38 a, 38 b and 38 c, respectively, are coupled to skirt region 34 and extend within lumen 31 of anchor 30. Posts 38 preferably are spaced 120° apart from one another about the circumference of anchor 30.

Anchor 30 preferably is fabricated by using self-expanding patterns (laser cut or chemically milled), braids and materials, such as a stainless steel, nickel-titanium (“Nitinol”) or cobalt chromium but alternatively may be fabricated using balloon-expandable patterns where the anchor is designed to plastically deform to it's final shape by means of balloon expansion. Replacement valve 20 is preferably from biologic tissues, e.g. porcine valve leaflets or bovine or equine pericardium tissues, alternatively it can be made from tissue engineered materials (such as extracellular matrix material from Small Intestinal Submucosa (SIS)) but alternatively may be prosthetic from an elastomeric polymer or silicone, Nitinol or stainless steel mesh or pattern (sputtered, chemically milled or laser cut). The leaflet may also be made of a composite of the elastomeric or silicone materials and metal alloys or other fibers such Kevlar or carbon. Annular base 22 of replacement valve 20 preferably is coupled to skirt region 34 of anchor 30, while commissures 24 of replacement valve leaflets 26 are coupled to posts 38.

Anchor 30 may be actuated using external non-hydraulic or non-pneumatic force to actively foreshorten in order to increase its radial strength. As shown below, the proximal and distal end regions of anchor 30 may be actuated independently. The anchor and valve may be placed and expanded in order to visualize their location with respect to the native valve and other anatomical features and to visualize operation of the valve. The anchor and valve may thereafter be repositioned and even retrieved into the delivery sheath or catheter. The apparatus may be delivered to the vicinity of the patients's aortic valve in a retrograde approach in a catheter having a diameter no more than 23 french, preferably no more than 21 french, more preferably no more than 19 french, or more preferably no more than 17 french. Upon deployment the anchor and replacement valve capture the native valve leaflets and positively lock to maintain configuration and position.

A deployment tool is used to actuate, reposition, lock and/or retrieve anchor 30. In order to avoid delivery of anchor 30 on a balloon for balloon expansion, a non-hydraulic or non-pneumatic anchor actuator is used. In this embodiment, the actuator is a deployment tool that includes distal region control wires 50, control rods or tubes 60 and proximal region control wires 62. Locks 40 include posts or arms 38 preferably with male interlocking elements 44 extending from skirt region 34 and mating female interlocking elements 42 in lip region 32. Male interlocking elements 44 have eyelets 45. Control wires 50 pass from a delivery system for apparatus 10 through female interlocking elements 42, through eyelets 45 of male interlocking elements 44, and back through female interlocking elements 42, such that a double strand of wire 50 passes through each female interlocking element 42 for manipulation by a medical practitioner external to the patient to actuate and control the anchor by changing the anchor's shape. Control wires 50 may comprise, for example, strands of suture.

Tubes 60 are reversibly coupled to apparatus 10 and may be used in conjunction with wires 50 to actuate anchor 30, e.g., to foreshorten and lock apparatus 10 in the fully deployed configuration. Tubes 60 also facilitate repositioning and retrieval of apparatus 10, as described hereinafter. For example, anchor 30 may be foreshortened and radially expanded by applying a distally directed force on tubes 60 while proximally retracting wires 50. As seen in FIGS. 3, control wires 62 pass through interior lumens 61 of tubes 60. This ensures that tubes 60 are aligned properly with apparatus 10 during deployment and foreshortening. Control wires 62 can also actuate anchor 60; proximally directed forces on control wires 62 contacts the proximal lip region 32 of anchor 30. Wires 62 also act to couple and decouple tubes 60 from apparatus 10. Wires 62 may comprise, for example, strands of suture.

FIGS. 1A and 2A illustrate anchor 30 in a delivery configuration or in a partially deployed configuration (e.g., after dynamic self-expansion expansion from a constrained delivery configuration within a delivery sheath). Anchor 30 has a relatively long length and a relatively small width in the delivery or partially deployed configuration, as compared to the foreshortened and fully deployed configuration of FIGS. 1B and 2B.

In FIGS. 1A and 2A, replacement valve 20 is collapsed within lumen 31 of anchor 30. Retraction of wires 50 relative to tubes 60 foreshortens anchor 30, which increases the anchor's width while decreasing its length. Such foreshortening also properly seats replacement valve 20 within lumen 31 of anchor 30. Imposed foreshortening will enhance radial force applied by apparatus 10 to surrounding tissue over at least a portion of anchor 30. In some embodiments, the anchor exerts an outward force on surrounding tissue to engage the tissue in such way to prevent migration of anchor caused by force of blood against closed leaflet during diastole. This anchoring force is preferably 1 to 2 lbs, more preferably 2 to 4 lbs, or more preferably 4 to 10 lbs. In some embodiments, the anchoring force is preferably greater than 1 pound, more preferably greater than 2 pounds, or more preferably greater than 4 pounds. Enhanced radial force of the anchor is also important for enhanced crush resistance of the anchor against the surrounding tissue due to the healing response (fibrosis and contraction of annulus over a longer period of time) or to dynamic changes of pressure and flow at each heart beat In an alternative embodiment, the anchor pattern or braid is designed to have gaps or areas where the native tissue is allowed to protrude through the anchor slightly (not shown) and as the foreshortening is applied, the tissue is trapped in the anchor. This feature would provide additional means to prevent anchor migration and enhance long term stability of the device.

Deployment of apparatus 10 is fully reversible until lock 40 has been locked via mating of male interlocking elements 44 with female interlocking elements 42. Deployment is then completed by decoupling tubes 60 from lip section 32 of anchor 30 by retracting one end of each wire 62 relative to the other end of the wire, and by retracting one end of each wire 50 relative to the other end of the wire until each wire has been removed from eyelet 45 of its corresponding male interlocking element 44.

As best seen in FIG. 2B, body region 36 of anchor 30 optionally may comprise barb elements 37 that protrude from anchor 30 in the fully deployed configuration, for example, for engagement of a patients's native valve leaflets and to preclude migration of the apparatus.

With reference now to FIGS. 3A and 3B, a delivery and deployment system for a self-expanding embodiment of apparatus 10 including a sheath 110 having a lumen 112. Self-expanding anchor 30 is collapsible to a delivery configuration within lumen 112 of sheath 110, such that apparatus 10 may be delivered via delivery system 100. As seen in FIG. 3A, apparatus 10 may be deployed from lumen 112 by retracting sheath 110 relative to apparatus 10, control wires 50 and tubes 60, which causes anchor 30 to dynamically self-expand to a partially deployed configuration. Control wires 50 then are retracted relative to apparatus 10 and tubes 60 to impose foreshortening upon anchor 30, as seen in FIG. 3B.

During foreshortening, tubes 60 push against lip region 32 of anchor 30, while wires 50 pull on posts 38 of the anchor. Wires 62 may be retracted along with wires 50 to enhance the distally-directed pushing force applied by tubes 60 to lip region 32. Continued retraction of wires 50 relative to tubes 60 would lock locks 40 and fully deploy apparatus 10 with replacement valve 20 properly seated within anchor 30, as in FIGS. 1B and 2B. Apparatus 10 comprises enhanced radial strength in the fully deployed configuration as compared to the partially deployed configuration of FIG. 3A. Once apparatus 10 has been fully deployed, wires 50 and 62 may be removed from apparatus 10, thereby separating delivery system 100 and tubes 60 from the apparatus.

Deployment of apparatus 10 is fully reversible until locks 40 have been actuated. For example, just prior to locking the position of the anchor and valve and the operation of the valve may be observed under fluoroscopy. If the position needs to be changed, by alternately relaxing and reapplying the proximally directed forces exerted by control wires 50 and/or control wires 62 and the distally directed forces exerted by tubes 60, expansion and contraction of the lip and skirt regions of anchor 30 may be independently controlled so that the anchor and valve can be moved to, e.g., avoid blocking the coronary ostia or impinging on the mitral valve. Apparatus 10 may also be completely retrieved within lumen 112 of sheath 110 by simultaneously proximally retracting wires 50 and tubes 60/wires 62 relative to sheath 110. Apparatus 10 then may be removed from the patient or repositioned for subsequent redeployment.

Referring now to FIGS. 4A-4F, step-by-step deployment of apparatus 10 via delivery system 100 is described. In FIG. 4A, sheath 110 is retracted relative to apparatus 10, wires 50 and tubes 60, thereby causing self-expandable anchor 30 to dynamically self-expand apparatus 10 from the collapsed delivery configuration within lumen 112 of sheath 110 to the partially deployed configuration. Apparatus 10 may then be dynamically repositioned via tubes 60 to properly orient the apparatus, e.g. relative to a patients's native valve leaflets.

In FIG. 4B, control wires 50 are retracted while tubes 60 are advanced, thereby urging lip region 32 of anchor 30 in a distal direction while urging posts 38 of the anchor in a proximal direction. This foreshortens apparatus 10, as seen in FIG. 4C. Deployment of apparatus 10 is fully reversible even after foreshortening has been initiated and has advanced to the point illustrated in FIG. 4C.

In FIG. 4D, continued foreshortening causes male interlocking elements 44 of locks 40 to engage female interlocking elements 42. The male elements mate with the female elements, thereby locking apparatus 10 in the foreshortened configuration, as seen in FIG. 4E. Wires 50 are then pulled through eyelets 45 of male elements 44 to remove the wires from apparatus 10, and wires 62 are pulled through the proximal end of anchor 30 to uncouple tubes 60 from the apparatus, thereby separating delivery system 100 from apparatus 10. Fully deployed apparatus

FIG. 4F.

Referring to FIGS. 5A-5F, a method of endovascularly replacing a patients's diseased aortic valve with apparatus 10 and delivery system 100 is described. As seen in FIG. 5A, sheath 110 of delivery system 100, having apparatus 10 disposed therein, is endovascularly advanced over guide wire G, preferably in a retrograde fashion (although an antegrade or hybrid approach alternatively may be used), through a patients's aorta A to the patients's diseased aortic valve AV. A nosecone 102 precedes sheath 110 in a known manner. In FIG. 5B, sheath 110 is positioned such that its distal region is disposed within left ventricle LV of the patients's heart H.

Apparatus 10 is deployed from lumen 112 of sheath 110, for example, under fluoroscopic guidance, such that anchor 30 of apparatus 10 dynamically self-expands to a partially deployed configuration, as in FIG. 5C. Advantageously, apparatus 10 may be retracted within lumen 112 of sheath 110 via wires 50—even after anchor 30 has dynamically expanded to the partially deployed configuration, for example, to abort the procedure or to reposition apparatus 10 or delivery system 100. As yet another advantage, apparatus 10 may be dynamically repositioned, e.g. via sheath 110 and/or tubes 60, in order to properly align the apparatus relative to anatomical landmarks, such as the patients's coronary ostia or the patients's native valve leaflets L. When properly aligned, skirt region 34 of anchor 30 preferably is disposed distal of the leaflets, while body region 36 is disposed across the leaflets and lip region 32 is disposed proximal of the leaflets.

Once properly aligned, wires 50 are retracted relative to tubes 60 to impose foreshortening upon anchor 30 and expand apparatus 10 to the fully deployed configuration, as in FIG. 5D. Foreshortening increases the radial strength of anchor 30 to ensure prolonged patency of valve annulus An, as well as to provide a better seal for apparatus 10 that reduces paravalvular regurgitation. As seen in FIG. 5E, locks 40 maintain imposed foreshortening. Replacement valve 20 is properly seated within anchor 30, and normal blood flow between left ventricle LV and aorta A is thereafter regulated by apparatus 10. Deployment of apparatus 10 advantageously is fully reversible until locks 40 have been actuated.

As seen in FIG. 5F, wires 50 are pulled from eyelets 45 of male elements 44 of locks 40, tubes 60 are decoupled from anchor 30, e.g. via wires 62, and delivery system 100 is removed from the patient, thereby completing deployment of apparatus 10. Optional barb elements 37 engage the patients's native valve leaflets, e.g. to preclude migration of the apparatus and/or reduce paravalvular regurgitation.

With reference now to FIGS. 6A-6F, a method of endovascularly replacing a patients's diseased aortic valve with apparatus 10 is provided, wherein proper positioning of the apparatus is ensured via positive registration of a modified delivery system to the patients's native valve leaflets. In FIG. 6A, modified delivery system 100′ delivers apparatus 10 to diseased aortic valve AV within sheath 110. As seen in FIGS. 6B and 6C, apparatus 10 is deployed from lumen 112 of sheath 110, for example, under fluoroscopic guidance, such that anchor 30 of apparatus

As when deployed via delivery system 100, deployment of apparatus 10 via delivery system 100′ is fully reversible until locks 40 have been actuated.

Delivery system 100′ comprises leaflet engagement element 120, which preferably self-expands along with anchor 30. Engagement element 120 is disposed between tubes 60 of delivery system 100′ and lip region 32 of anchor 30. Element 120 releasably engages the anchor. As seen in FIG. 6C, the element is initially deployed proximal of the patients's native valve leaflets L. Apparatus 10 and element 120 then may be advanced/dynamically repositioned until engagement element positively registers against the leaflets, thereby ensuring proper positioning of apparatus 10. Also delivery system 100′ includes filter structure 61A (e.g., filter membrane or braid) as part of push tubes 60 to act as an embolic protection element. Emboli can be generated during manipulation and placement of anchor from either diseased native leaflet or surrounding aortic tissue and can cause blockage. Arrows 61B in FIG. 6E show blood flow through filter structure 61A where blood is allowed to flow but emboli is trapped in the delivery system and removed with it at the end of the procedure.

Alternatively, foreshortening may be imposed upon anchor 30 while element 120 is disposed proximal of the leaflets, as in FIG. 6D. Upon positive registration of element 120 against leaflets L, element 120 precludes further distal migration of apparatus 10 during additional foreshortening, thereby reducing a risk of improperly positioning the apparatus. FIG. 6E details engagement of element 120 against the native leaflets. As seen in FIG. 6F, once apparatus 10 is fully deployed, element 120, wires 50 and tubes 60 are decoupled from the apparatus, and delivery system 100′ is removed from the patient, thereby completing the procedure.

With reference to FIG. 7, an alternative embodiment of the apparatus of FIGS. 6 is described, wherein leaflet engagement element 120 is coupled to anchor 30 of apparatus 10′, rather than to delivery system 100. Engagement element 120 remains implanted in the patient post-deployment of apparatus 10′. Leaflets L are sandwiched between lip region 32 of anchor 30 and element 120 in the fully deployed configuration. In this manner, element 120 positively registers apparatus 10′ relative to the leaflets and precludes distal migration of the apparatus over time.

Referring now to FIGS. 8A-8C, an alternative delivery system adapted for use with a balloon expandable embodiment of the present invention is described. In FIG. 8A, apparatus 10″ comprises anchor 30′ that may be fabricated from balloon-expandable materials. Delivery system 100″ comprises inflatable member 130 disposed in a deflated configuration within lumen 31 of anchor 30′. In FIG. 8B, optional outer sheath 110 is retracted, and inflatable member 130 is inflated to expand anchor 30′ to the fully deployed configuration. As inflatable member 130 is being deflated, as in earlier embodiments, wires 50 and 62 and tubes 60 may be used to assist deployment of anchor 30′ and actuation of locks 40, as well as to provide reversibility and retrievability of apparatus 10″ prior to actuation of locks 40. Next, wires 50 and 62 and tubes 60 are removed from apparatus 10″, and delivery system 100″ is removed, as seen in FIG. 8C.

As an alternative delivery method, anchor 30′ may be partially deployed via partial expansion of inflatable member 130. The inflatable member would then be advanced within replacement valve 20 prior to inflation of inflatable member 130 and full deployment of apparatus 10″. Inflation pressures used will range from about 3 to 6 atm, or more preferably from about 4 to 5 atm, though higher and lower atm pressures may also be used (e.g., greater than 3 atm, more preferably greater than 4 atm, more preferably greater than 5 atm, or more preferably greater than 6 atm). Advantageously, separation of inflatable member 130 from replacement valve 20, until partial deployment of apparatus 10″ at a treatment site, is expected to reduce a delivery profile of the apparatus, as compared to previously known apparatus. This profile reduction may facilitate retrograde delivery and deployment of apparatus 10″, even when anchor 30′ is balloon-expandable.

Although anchor 30′ has illustratively been described as fabricated from balloon-expandable materials, it should be understood that anchor 30′ alternatively may be fabricated from self-expanding materials whose expansion optionally may be balloon-assisted. In such a configuration, anchor 30′ would expand to a partially deployed configuration upon removal of outer sheath 110. If required, inflatable member 130 then would be advanced within replacement valve 20 prior to inflation. Inflatable member 130 would assist full deployment of apparatus 10″, for example, when the radial force required to overcome resistance from impinging tissue were too great to be overcome simply by manipulation of wires 50 and tubes 60. Advantageously, optional placement of inflatable member 130 within replacement valve 20, only after dynamic self-expansion of apparatus 10″ to the partially deployed configuration at a treatment site, is expected to reduce a delivery profile of the apparatus, as compared to previously known apparatus. This reduction may facilitate retrograde delivery and deployment of apparatus 10″.

With reference to FIGS. 9A-H and 10, methods and apparatus for a balloon-assisted embodiment of the present invention are described in greater detail. FIGS. 9A-H and 10 illustratively show apparatus 10′ of FIG. 7 used in combination with delivery system 100″ of FIGS. 8A-C. FIG. 10 illustrates a sectional view of delivery system 100″. Inner shaft 132 of inflatable member 130 preferably is about 4 Fr in diameter, and comprises lumen 133 configured for passage of guidewire G, having a diameter of about 0.035″, therethrough. Push tubes 60 and pull wires 50 pass through guidetube 140, which preferably has a diameter of about 15 Fr or smaller. Guide tube 140 is disposed within lumen 112 of outer sheath 110, which preferably has a diameter of about 17 Fr or smaller.

In FIG. 9A, apparatus 10′ is delivered to diseased aortic valve AV within lumen 112 of sheath 110. In FIG. 9B, sheath 110 is retracted relative to apparatus 10′ to dynamically self-expand the apparatus to the partially deployed configuration. Also retracted and removed is nosecone 102 which is attached to a pre-slit lumen (not shown) that facilitates its removal prior to loading and advancing of a regular angioplasty balloon catheter over guidewire and inside delivery system 110.

In FIG. 9C, pull wires 50 and push tubes 60 are manipulated from external to the patient to foreshorten anchor 30 and sufficiently expand lumen 31 of the anchor to facilitate advancement of inflatable member 130 within replacement valve 20. Also shown is the tip of an angioplasty catheter 130 being advanced through delivery system 110.

The angioplasty balloon catheter or inflatable member 130 then is advanced within the replacement valve, as in FIG. 9D, and additional foreshortening is imposed upon anchor 30 to actuate locks 40, as in FIG. 9E. The inflatable member is inflated to further displace the patients's native valve leaflets L and ensure adequate blood flow through, and long-term patency of, replacement valve 20, as in FIG. 9F. Inflatable member 130 then is deflated and removed from the patient, as in FIG. 9G. A different size angioplasty balloon catheter could be used repeat the same step if deemed necessary by the user. Push tubes 60 optionally may be used to further set leaflet engagement element 120, or optional barbs B along posts 38, more deeply within leaflets L, as in FIG. 9H. Then, delivery system 100″ is removed from the patient, thereby completing percutaneous heart valve replacement.

As will be apparent to those of skill in the art, the order of imposed foreshortening and balloon expansion described in FIGS. 9A-H and 10 is only provided for the sake of illustration. The actual order may vary according to the needs of a given patient and/or the preferences of a given medical practitioner. Furthermore, balloon-assist may not be required in all instances, and the inflatable member may act merely as a safety precaution employed selectively in challenging clinical cases.

Referring now to FIGS. 11A-11C, alternative locks for use with apparatus of the present invention are described. In FIG. 11A, lock 40′ comprises male interlocking element 44 as described previously. However, female interlocking element 42′ illustratively comprises a triangular shape, as compared to the round shape of interlocking element 42 described previously. The triangular shape of female interlocking element 42′ may facilitate mating of male interlocking element 44 with the female interlocking element without necessitating deformation of the male interlocking element.

In FIG. 1B, lock 40″ comprises alternative male interlocking element 44′ having multiple in-line arrowheads 46 along posts 38. Each arrowhead comprises resiliently deformable appendages 48 to facilitate passage through female interlocking element 42. Appendages 48 optionally comprise eyelets 49, such that control wire 50 or a secondary wire may pass therethrough to constrain the appendages in the deformed configuration. To actuate lock 40″, one or more arrowheads 46 of male interlocking element 44′ are drawn through female interlocking element 42, and the wire is removed from eyelets 49, thereby causing appendages 48 to resiliently expand and actuate lock 40″.

Advantageously, providing multiple arrowheads 46 along posts 38 yields a ratchet that facilitates in-vivo determination of a degree of foreshortening imposed upon apparatus of the present invention. Furthermore, optionally constraining appendages 48 of arrowheads 46 via eyelets 49 prevents actuation of lock 40″ (and thus deployment of apparatus of the present invention) even after male element 44′ has been advanced through female element 42. Only after a medical practitioner has removed the wire constraining appendages 48 is lock 40″ fully engaged and deployment no longer reversible.

Lock 40′″ of FIG. 11C is similar to lock 40″ of FIG. 1B, except that optional eyelets 49 on appendages 48 have been replaced by optional overtube 47. Overtube 47 serves a similar function to eyelets 49 by constraining appendages 48 to prevent locking until a medical practitioner has determined that apparatus of the present invention has been foreshortened and positioned adequately at a treatment site. Overtube 47 is then removed, which causes the appendages to resiliently expand, thereby fully actuating lock 40′″.

With reference to FIGS. 12A-12C, an alternative locking mechanism is described that is configured to engage the patients's aorta. Male interlocking elements 44″ of locks 40″ ″ comprise arrowheads 46′ having sharpened appendages 48′. Upon expansion from the delivery configuration of FIG. 12A to the foreshortened configuration of FIG. 12B, apparatus 10 positions sharpened appendages 48′ adjacent the patients's aorta A. Appendages 48′ engage the aortic wall and reduce a risk of device migration over time.

With reference now to FIG. 13, a risk of paravalvular leakage or regurgitation around apparatus of the present invention is described. In FIG. 13, apparatus 10 has been implanted at the site of diseased aortic valve AV, for example, using techniques described hereinabove. The surface of native valve leaflets L is irregular, and interface I between leaflets L and anchor 30 may comprise gaps where blood B may seep through. Such leakage poses a risk of blood clot formation or insufficient blood flow.

Referring to FIG. 14, optional elements for reducing regurgitation or leakage are described. Compliant sacs 200 may be disposed about the exterior of anchor 30 to provide a more efficient seal along irregular interface 1. Sacs 200 may be filled with an appropriate material, for example, water, blood, foam or a hydrogel. Alternative fill materials will be apparent.

With reference to FIGS. 15A-E, illustrative arrangements for sacs 200 are provided. In FIG. 15A, sacs 200 are provided as discrete sacs at different positions along the height of anchor 30. In FIG. 15B, the sacs are provided as continuous cylinders at various heights. In FIG. 15C, a single sac is provided with a cylindrical shape that spans multiple heights. The sacs of FIG. 15D are discrete, smaller and provided in larger quantities. FIG. 15E provides a spiral sac. Alternative sac configurations will be apparent to those of skill in the art.

With reference to FIGS. 16A-16C, exemplary techniques for fabricating sacs 200 are provided. In FIG. 16A, sacs 20 comprise ‘fish-scale’ slots 202 that may be back-filled, for example, with ambient blood passing through replacement valve 20. In FIG. 16B, the sacs comprise pores 204 that may be used to fill the sacs. In FIG. 16C, the sacs open to lumen 31 of anchor 30 and are filled by blood washing past the sacs as the blood moves through apparatus 10.

FIGS. 17A-17B and 18A-18B show yet another alternative embodiment of the anchor lock. Anchor 300 has a plurality of male interlocking elements 302 having eyelets 304 formed therein. Male interlocking elements are connected to braided structure 300 by inter-weaving elements 302 (and 308) or alternatively suturing, soldering, welding, or connecting with adhesive. Valve commissures 24 are connected to male interlocking elements 302 along their length. Replacement valve 20 annular base 22 is connected to the distal end 34 of anchor 300 (or 30) as is illustrated in FIGS. 1A and 1B. Male interlocking elements 302 also include holes 306 that mate with tabs 310 extending into holes 312 in female interlocking elements 308. To lock, control wires 314 passing through eyelets 304 and holes 312 are pulled proximally with respect to the proximal end of braided anchor 300 to draw the male interlocking elements through holes 312 so that tabs 310 engage holes 306 in male interlocking elements 302. Also shown is release wires 314B that passes through eylet 304B in female interlocking element 308. If needed, during the procedure, the user may pull on release wires 314B reversing orientation of tabs 310 releasing the anchor and allowing for repositioning of the device or it3 s removal from the patient. Only when final positioning as desired by the operating physician, would release wire 314B and control wire 314 are cut and removed from the patient with the delivery system.

FIGS. 19-21 show an alternative way of releasing the connection between the anchor and its actuating tubes and control wires. Control wires 62 extend through tubes 60 from outside the patient, loop through the proximal region of anchor 30 and extend partially back into tube 60. The doubled up portion of control wire 62 creates a force fit within tube 60 that maintains the control wire's position with respect to tube 60 when all control wires 62 are pulled proximally to place a proximally directed force on anchor 30. When a single control wire 62 is pulled proximally, however, the frictional fit between that control wire and the tube in which it is disposed is overcome, enabling the end 63 of control wire 62 to pull free of the tube, as shown in FIG. 21, thereby releasing anchor 30.

FIGS. 22-24 show an alternative embodiment of the anchor. Anchor 350 is made of a metal braid, such as Nitinol or stainless steel. A replacement valve 354 is disposed within anchor 350. Anchor 350 is actuated in substantially the same way as anchor 30 of FIGS. 1-4 through the application of proximally and distally directed forces from control wires (not shown) and tubes 352.

FIGS. 25 and 26 show yet another embodiment of the delivery and deployment apparatus of the invention. As an alternative to the balloon expansion method described with respect to FIGS. 8A-C, in this embodiment the nosecone (e.g., element 102 of FIGS. 5A-F) is replaced by an angioplasty balloon catheter 360. Thus, expandable balloon catheter 360 precedes sheath 110 on guidewire G. When anchor 30 and valve 20 are expanded through the operation of tubes 60 and the control wires (not shown) as described above, balloon catheter 360 is retracted proximally within the expanded anchor and valve and expanded further as described above with respect to FIGS. 8A-C.

FIGS. 27-31 show seals 370 that expand over time to seal the interface between the anchor and valve and the patients's tissue. Seals 370 are preferably formed from Nitinol wire surrounded by an expandable foam. As shown in cross-section in FIGS. 28 and 29, at the time of deployment, the foam 372 is compressed about the wire 374 and held in the compressed form by a time-released coating 376. After deployment, coating 376 dissolves in vivo to allow foam 372 to expand, as shown in FIGS. 30 and 31.

FIGS. 32-34 show another way to seal the replacement valve against leakage. A fabric seal 380 extends from the distal end of valve 20 and back proximally over anchor 30 during delivery. When deployed, as shown in FIGS. 33 and 34, fabric seal 380 bunches up to create fabric flaps and pockets that extend into spaces formed by the native valve leaflets 382, particularly when the pockets are filled with blood in response to backflow blood pressure. This arrangement creates a seal around the replacement valve.

FIGS. 35A-H show another embodiment of a replacement heart valve apparatus in accordance with the present invention. Apparatus 450 comprises replacement valve 460 (see FIGS. 37B and 38C) disposed within and coupled to anchor 470. Replacement valve 460 is preferably biologic, e.g. porcine, but alternatively may be synthetic. Anchor 470 preferably is fabricated from self-expanding materials, such as a stainless steel wire mesh or a nickel-titanium alloy (“Nitinol”), and comprises lip region 472, skirt region 474, and body regions 476 a, 476 b and 476 c. Replacement valve 460 preferably is coupled to skirt region 474, but alternatively may be coupled to other regions of the anchor. As described hereinbelow, lip region 472 and skirt region 474 are configured to expand and engage/capture a patients's native valve leaflets, thereby providing positive registration, reducing paravalvular regurgitation, reducing device migration, etc.

As seen in FIG. 35A, apparatus 450 is collapsible to a delivery configuration, wherein the apparatus may be delivered via delivery system 410. Delivery system 410 comprises sheath 420 having lumen 422, as well as wires 424 a and 424 b seen in FIGS. 35D-35G. Wires 424 a are configured to expand skirt region 474 of anchor 470, as well as replacement valve 460 coupled thereto, while wires 424 b are configured to expand lip region 472.

As seen in FIG. 35B, apparatus 450 may be delivered and deployed from lumen 422 of catheter 420 while the apparatus is disposed in the collapsed delivery configuration. As seen in FIGS. 35B-35D, catheter 420 is retracted relative to apparatus 450, which causes anchor 470 to dynamically self-expand to a partially deployed configuration. Wires 424 a are then retracted to expand skirt region 474, as seen in FIGS. 35E and 35F. Preferably, such expansion may be maintained via locking features described hereinafter.

In FIG. 35G, wires 424 b are retracted to expand lip region 472 and fully deploy apparatus 450. As with skirt region 474, expansion of lip region 472 preferably may be maintained via locking features. After both lip region 472 and skirt region 474 have been expanded, wires 424 may be removed from apparatus 450, thereby separating delivery system 410 from the apparatus. Delivery system 410 then may be removed, as seen in FIG. 35H.

As will be apparent to those of skill in the art, lip region 472 optionally may be expanded prior to expansion of skirt region 474. As yet another alternative, lip region 472 and skirt region 474 optionally may be expanded simultaneously, in parallel, in a step-wise fashion or sequentially. Advantageously, delivery of apparatus 450 is fully reversible until lip region 472 or skirt region 474 has been locked in the expanded configuration.

With reference now to FIGS. 36A-E, individual cells of anchor 470 of apparatus 450 are described to detail deployment and expansion of the apparatus. In FIG. 36A, individual cells of lip region 472, skirt region 474 and body regions 476 a, 476 b and 476 c are shown in the collapsed delivery configuration, as they would appear while disposed within lumen 422 of sheath 420 of delivery system 410 of FIGS. 35A-H. A portion of the cells forming body regions 476, for example, every ‘nth’ row of cells, comprises locking features.

Body region 476 a comprises male interlocking element 482 of lip lock 480, while body region 476 b comprises female interlocking element 484 of lip lock 480. Male element 482 comprises eyelet 483. Wire 424 b passes from female interlocking element 484 through eyelet 483 and back through female interlocking element 484, such that there is a double strand of wire 424 b that passes through lumen 422 of catheter 420 for manipulation by a medical practitioner external to the patient. Body region 476 b further comprises male interlocking element 492 of skirt lock 490, while body region 476 c comprises female interlocking element 494 of the skirt lock. Wire 424 a passes from female interlocking element 494 through eyelet 493 of male interlocking element 492, and back through female interlocking element 494. Lip lock 480 is configured to maintain expansion of lip region 472, while skirt lock 490 is configured to maintain expansion of skirt region 474.

In FIG. 36B, anchor 470 is shown in the partially deployed configuration, e.g., after deployment from lumen 422 of sheath 420. Body regions 476, as well as lip region 472 and skirt region 474, self-expand to the partially deployed configuration. Full deployment is then achieved by retracting wires 424 relative to anchor 470, and expanding lip region 472 and skirt region 474 outward, as seen in FIGS. 36C and 36D. As seen in FIG. 36E, expansion continues until the male elements engage the female interlocking elements of lip lock 480 and skirt lock 490, thereby maintaining such expansion (lip lock 480 shown in FIG. 36E). Advantageously, deployment of apparatus 450 is fully reversible until lip lock 480 and/or skirt lock 490 has been actuated.

With reference to FIGS. 37A-B, isometric views, partially in section, further illustrate apparatus 450 in the fully deployed and expanded configuration. FIG. 37A illustrates the wireframe structure of anchor 470, while FIG. 37B illustrates an embodiment of anchor 470 covered in a biocompatible material B. Placement of replacement valve 460 within apparatus 450 may be seen in FIG. 37B. The patients's native valve is captured between lip region 472 and skirt region 474 of anchor 470 in the fully deployed configuration (see FIG. 38B).

Referring to FIGS. 38A-C, in conjunction with FIGS. 35 and 36, a method for endovascularly replacing a patients's diseased aortic valve with apparatus 450 is described. Delivery system 410, having apparatus 450 disposed therein, is endovascularly advanced, preferably in a retrograde fashion, through a patients's aorta A to the patients's diseased aortic valve AV. Sheath 420 is positioned such that its distal end is disposed within left ventricle LV of the patients's heart H. As described with respect to FIGS. 35, apparatus 450 is deployed from lumen 422 of sheath 420, for example, under fluoroscopic guidance, such that skirt section 474 is disposed within left ventricle LV, body section 476 b is disposed across the patients's native valve leaflets L, and lip section 472 is disposed within the patients's aorta A. Advantageously, apparatus 450 may be dynamically repositioned to obtain proper alignment with the anatomical landmarks. Furthermore, apparatus 450 may be retracted within lumen 422 of sheath 420 via wires 424, even after anchor 470 has dynamically expanded to the partially deployed configuration, for example, to abort the procedure or to reposition sheath 420.

Once properly positioned, wires 424 a are retracted to expand skirt region 474 of anchor 470 within left ventricle LV. Skirt region 474 is locked in the expanded configuration via skirt lock 490, as previously described with respect to FIGS. 36A-E. In FIG. 38A, skirt region 474 is maneuvered such that it engages the patients's valve annulus An and/or native valve leaflets L, thereby providing positive registration of apparatus 450 relative to the anatomical landmarks.

Wires 424 b are then actuated external to the patient in order to expand lip region 472, as previously described in FIGS. 35A-H. Lip region 472 is locked in the expanded configuration via lip lock 480. Advantageously, deployment of apparatus 450 is fully reversible until lip lock 480 and/or skirt lock 490 has been actuated. Wires 424 are pulled from eyelets 483 and 493, and delivery system 410 is removed from the patient. As will be apparent, the order of expansion of lip region 472 and skirt region 474 may be reversed, concurrent, etc.

As seen in FIG. 38B, lip region 472 engages the patients's native valve leaflets L, thereby providing additional positive registration and reducing a risk of lip region 472 blocking the patients's coronary ostia O. FIG. 38C illustrates the same in cross-sectional view, while also showing the position of replacement valve 460. The patients's native leaflets are engaged and/or captured between lip region 472 and skirt region 474. Advantageously, lip region 472 precludes distal migration of apparatus 450, while skirt region 474 precludes proximal migration. It is expected that lip region 472 and skirt region 474 also will reduce paravalvular regurgitation.

With reference to FIGS. 39-41, a first embodiment of two-piece apparatus of the present invention adapted for percutaneous replacement of a patients's heart valve is described. As seen in FIGS. 41, apparatus 510 comprises a two-piece device having custom-designed expandable anchor piece 550 of FIGS. 39A-B and expandable replacement valve piece 600 of FIGS. 40A-B. Both anchor piece 550 and valve piece 600 have reduced delivery configurations and expanded deployed configurations. Both may be either balloon expandable (e.g. fabricated from a stainless steel) or self-expanding (e.g. fabricated from a nickel-titanium alloy (“Nitinol”) or from a wire mesh) from the delivery to the deployed configurations.

When replacing a patients's aortic valve, apparatus 510 preferably may be delivered through the patients's aorta without requiring a transseptal approach, thereby reducing patient trauma, complications and recovery time. Furthermore, apparatus 510 enables dynamic repositioning of anchor piece 550 during delivery and facilitates positive registration of apparatus 510 relative to the native position of the patients's valve, thereby reducing a risk of device migration and reducing a risk of blocking or impeding flow to the patients's coronary ostia. Furthermore, the expanded deployed configuration of apparatus 510, as seen in FIG. 41D, is adapted to reduce paravalvular regurgitation, as well as to facilitate proper seating of valve piece 600 within anchor piece 550.

As seen in FIGS. 39A-B, anchor piece 550 preferably comprises three sections. Lip section 560 is adapted to engage the patients's native valve leaflets to provide positive registration and ensure accurate placement of the anchor relative to the patients's valve annulus during deployment, while allowing for dynamic repositioning of the anchor during deployment. Lip section 560 also maintains proper positioning of composite anchor/valve apparatus 510 post-deployment to preclude distal migration. Lip section 560 optionally may be covered or coated with biocompatible film B (see FIGS. 41A-D) to ensure engagement of the native valve leaflets. It is expected that covering lip section 560 with film B especially would be indicated when the native leaflets are stenosed and/or fused together

Groove section 570 of anchor piece 550 is adapted to engage an expandable frame portion, described hereinbelow, of valve piece 600 to couple anchor piece 550 to valve piece 600. As compared to previously known apparatus, groove section 570 comprises additional material and reduced openings or gaps G, which is expected to reduce tissue protrusion through the gaps upon deployment, thereby facilitating proper seating of the valve within the anchor. Groove section 570 optionally may be covered or coated with biocompatible film B (see FIGS. 41A-D) to further reduce native valve tissue protrusion through gaps G.

Finally, skirt section 580 of anchor piece 550 maintains proper positioning of composite anchor/valve apparatus 510 post-deployment by precluding proximal migration. When replacing a patients's aortic valve, skirt section 580 is deployed within the patients's left ventricle. As with lip section 560 and groove section 570, skirt section 580 optionally may be covered or coated with biocompatible film B (see FIGS. 41) to reduce paravalvular regurgitation. As will be apparent to those of skill in the art, all, a portion of, or none of anchor piece 50 may be covered or coated with biocompatible film B.

In FIG. 39A, a portion of anchor piece 550 has been flattened out to illustrate the basic anchor cell structure, as well as to illustrate techniques for manufacturing anchor piece 550. In order to form the entire anchor, anchor 550 would be bent at the locations indicated in FIG. 39A, and the basic anchor cell structure would be revolved to form ajoined 360° structure. Lip section 560 would be bent back into the page to form a lip that doubles over the groove section, groove section 570 would be bent out of the page into a ° ‘C’—or ‘U’-shaped groove, while skirt section 580 would be bent back into the page. FIG. 39B shows the anchor portion after bending and in an expanded deployed configuration.

The basic anchor cell structure seen in FIG. 39A is preferably formed through laser cutting of a flat sheet or of a hollow tube placed on a mandrel. When formed from a flat sheet, the sheet would be cut to the required number of anchor cells, bent to the proper shape, and revolved to form a cylinder. The ends of the cylinder would then be joined together, for example, by heat welding.

If balloon expandable, anchor piece 550 would be formed from an appropriate material, such as stainless steel, and then crimped onto a balloon delivery catheter in a collapsed delivery configuration. If self-expanding and formed from a shape-memory material, such as a nickel-titanium alloy (“Nitinol”), the anchor piece would be heat-set such that it could be constrained within a sheath in the collapsed delivery configuration, and then would dynamically self-expand to the expanded deployed configuration upon removal of the sheath. Likewise, if anchor piece 550 were formed from a wire mesh or braid, such as a spring steel braid, the anchor would be constrained within a sheath in the delivery configuration and dynamically expanded to the deployed configuration upon removal of the sheath.

In FIGS. 40A-40B, valve piece 600 is described in greater detail. FIG. 40A illustrates valve piece 600 in a collapsed delivery configuration, while FIG. 40B illustrates the valve piece in an expanded deployed configuration. Valve piece 600 comprises replacement valve 610 coupled to expandable frame 620. Replacement valve 610 is preferably biologic, although synthetic valves may also be used. Replacement valve 610 preferably comprises three leaflets 611 coupled to three posts 621 of expandable frame 620. Expandable frame 620 is preferably formed from a continuous piece of material and may comprise tips 622 in the collapsed delivery configuration, which expand to form hoop 624 in the deployed configuration. Hoop 624 is adapted to engage groove section 570 of anchor piece 550 for coupling anchor piece 550 to valve piece 600. As with anchor piece 550, valve piece 600 may be balloon expandable and coupled to a balloon delivery catheter in the delivery configuration. Alternatively, anchor piece 550 may be self-expanding, e.g. Nitinol or wire mesh, and constrained within a sheath in the delivery configuration.

Referring again to FIGS. 41A-41D, a method for deploying valve piece 600 and coupling it to deployed anchor piece 550 to form two-piece apparatus 510 is described. In FIG. 41A, valve piece 600 is advanced within anchor piece 550 in an at least partially compressed delivery configuration. In FIG. 41B, tips 622 of frame 620 are expanded such that they engage groove section 570 of anchor piece 550. In FIG. 41C, frame 620 continues to expand and form hoop 624. Hoop 624 flares out from the remainder of valve piece 600 and acts to properly locate the hoop within groove section 570. FIG. 41D shows valve piece 600 in a fully deployed configuration, properly seated and friction locked within groove section 570 to form composite anchor/valve apparatus 510.

Anchor piece 550 and valve piece 600 of apparatus 510 preferably are spaced apart and releasably coupled to a single delivery catheter while disposed in their reduced delivery configurations. Spacing the anchor and valve apart reduces a delivery profile of the device, thereby enabling delivery through a patients's aorta without requiring a transseptal approach. With reference to FIG. 42, a first embodiment of single catheter delivery system 700 for use with apparatus 510 is described. Delivery system 700 is adapted for use with a preferred self-expanding embodiment of apparatus 510.

Delivery system 700 comprises delivery catheter 710 having inner tube 720, middle distal tube 730, and outer tube 740. Inner tube 720 comprises lumen 722 adapted for advancement over a standard guide wire, per se known. Middle distal tube 730 is coaxially disposed about a distal region of inner tube 720 and is coupled to a distal end 724 of the inner tube, thereby forming proximally-oriented annular bore 732 between inner tube 720 and middle tube 730 at a distal region of delivery catheter 710. Outer tube 740 is coaxially disposed about inner tube 720 and extends from a proximal region of the inner tube to a position at least partially coaxially overlapping middle distal tube 730. Outer tube 740 preferably comprises distal step 742, wherein lumen 743 of outer tube 740 is of increased diameter. Distal step 742 may overlap middle distal tube 730 and may also facilitate deployment of valve piece 600, as described hereinbelow with respect to FIGS. 45A-45I.

Proximally-oriented annular bore 732 between inner tube 720 and middle distal tube 730 is adapted to receive skirt section 580 and groove section 570 of anchor piece 550 in the reduced delivery configuration. Annular space 744 formed at the overlap between middle distal tube 730 and outer tube 740 is adapted to receive lip section 560 of anchor piece 550 in the reduced delivery configuration. More proximal annular space 746 between inner tube 720 and outer tube 740 may be adapted to receive replacement valve 610 and expandable frame 620 of valve piece 600 in the reduced delivery configuration.

Inner tube 720 optionally may comprise retainer elements 726 a and 726 b to reduce migration of valve piece 600. Retainer elements 726 preferably are fabricated from a radiopaque material, such as platinum-iridium or gold, to facilitate deployment of valve piece 600, as well as coupling of the valve piece to anchor piece 550. Additional or alternative radiopaque elements may be disposed at other locations about delivery system 700 or apparatus 510, for example, in the vicinity of anchor piece 550.

With reference now to FIG. 43, an alternative delivery system for use with apparatus of the present invention is described. Delivery system 750 comprises two distinct catheters adapted to deliver the anchor and valve pieces, respectively: anchor delivery catheter 710′ and valve delivery catheter 760. In use, catheters 710′ and 760 may be advanced sequentially to a patients's diseased heart valve for sequential deployment and coupling of anchor piece 550 to valve piece 600 to form composite two-piece apparatus 510.

Delivery catheter 710′ is substantially equivalent to catheter 710 described hereinabove, except that catheter 710′ does not comprise retainer elements 726, and annular space 746 does not receive valve piece 600. Rather, valve piece 600 is received within catheter 760 in the collapsed delivery configuration. Catheter 760 comprises inner tube 770 and outer tube 780. Inner tube 770 comprises lumen 772 for advancement of catheter 760 over a guide wire. The inner tube optionally may also comprise retainer elements 774 a and 774 b, e.g. radiopaque retainer elements 774, to reduce migration of valve piece 600. Outer tube 780 is coaxially disposed about inner tuber 770 and preferably comprises distal step 782 to facilitate deployment and coupling of valve piece 600 to anchor piece 550, as described hereinbelow. Valve piece 600 may be received in annular space 776 between inner tube 770 and outer tube 780, and more preferably may be received within annular space 776 between retainer elements 774.

Referring now to FIG. 44, another alternative delivery system is described. As discussed previously, either anchor piece 550 or valve piece 600 (or portions thereof or both) may be balloon expandable from the delivery configuration to the deployed configuration. Delivery system 800 is adapted for delivery of an embodiment of apparatus 510 wherein the valve piece is balloon expandable. Additional delivery systems—both single and multi-catheter—for deployment of alternative combinations of balloon and self-expandable elements of apparatus of the present invention will be apparent to those of skill in the art in view of the illustrative delivery systems provided in FIGS. 42-44.

In FIG. 44, delivery system 800 comprises delivery catheter 710″. Delivery catheter 710″ is substantially equivalent to delivery catheter 710 of delivery system 700, except that catheter 710″ does not comprise retainer elements 726, and annular space 746 does not receive the valve piece. Additionally, catheter 710″ comprises inflatable balloon 802 coupled to the exterior of outer tube 740″, as well as an inflation lumen (not shown) for reversibly delivering an inflation medium from a proximal region of catheter 710″ into the interior of inflatable balloon 802 for expanding the balloon from a delivery configuration to a deployed configuration. Valve piece 600 may be crimped to the exterior of balloon 802 in the delivery configuration, then deployed and coupled to anchor piece 550 in vivo. Delivery catheter 710″ preferably comprises radiopaque marker bands 804 a and 804 b disposed on either side of balloon 802 to facilitate proper positioning of valve piece 600 during deployment of the valve piece, for example, under fluoroscopic guidance.

With reference now to FIGS. 45A-45H, in conjunction with FIGS. 39-42, an illustrative method of endovascularly replacing a patients's diseased heart valve using apparatus of the present invention is described. In FIG. 45A, a distal region of delivery system 700 of FIG. 42 has been delivered through a patients's aorta A, e.g., over a guide wire and under fluoroscopic guidance using well-known percutaneous techniques, to a vicinity of diseased aortic valve AV of heart H. Apparatus 510 of FIGS. 39-41 is disposed in the collapsed delivery configuration within delivery catheter 710 with groove section 570 and skirt section 580 of anchor piece 550 collapsed within annular bore 732, and lip section 560 of anchor piece 550 collapsed within annular space 744. Valve piece 600 is disposed in the collapsed delivery configuration between retainer elements 726 within more proximal annular space 746. Separation of anchor piece 550 and valve piece 600 of apparatus 510 along the longitudinal axis of delivery catheter 710 enables percutaneous aortic delivery of apparatus 510 without requiring a transseptal approach.

Aortic valve AV comprises native valve leaflets L attached to valve annulus An. Coronary ostia O are disposed just proximal of diseased aortic valve AV. Coronary ostia O connect the patients's coronary arteries to aorta A and are the conduits through which the patients's heart muscle receives oxygenated blood. As such, it is critical that the ostia remain unobstructed post-deployment of apparatus 510.

In FIG. 45A, a distal end of delivery catheter 710 has been delivered across diseased aortic valve AV into the patients's left ventricle LV. As seen in FIG. 45B, outer tube 740 is then retracted proximally relative to inner tube 720 and middle distal tube 730. Outer tube 740 no longer coaxially overlaps middle distal tube 730, and lip section 560 of anchor piece 550 is removed from annular space 744. Lip section 560 self-expands to the deployed configuration. As seen in FIG. 45C, inner tube 720 and middle tube 730 (or all of delivery catheter 710) are then distally advanced until lip section 560 engages the patients's native valve leaflets L, thereby providing positive registration of anchor piece 550 to leaflets L. Registration may be confirmed, for example, via fluoroscopic imaging of radiopaque features coupled to apparatus 510 or delivery system 700 and/or via resistance encountered by the medical practitioner distally advancing anchor piece 550.

Lip section 560 may be dynamically repositioned until it properly engages the valve leaflets, thereby ensuring proper positioning of anchor piece 550 relative to the native coronary ostia O, as well as the valve annulus An, prior to deployment of groove section 570 and skirt section 580. Such multi-step deployment of anchor piece 550 enables positive registration and dynamic repositioning of the anchor piece. This is in contrast to previously known percutaneous valve replacement apparatus.

As seen in FIG. 45D, once leaflets L have been engaged by lip section 560 of anchor piece 550, inner tube 720 and middle distal tube 730 are further distally advanced within left ventricle LV, while outer tube 740 remains substantially stationary. Lip section 560, engaged by leaflets L, precludes further distal advancement/migration of anchor piece 550. As such, groove section 570 and skirt section 580 are pulled out of proximally-oriented annular bore 732 between inner tube 720 and middle distal tube 730 when the tubes are distally advanced. The groove and skirt sections self-expand to the deployed configuration, as seen in FIG. 45E. Groove section 570 pushes native valve leaflets L and lip section 560 against valve annulus An, while skirt section 580 seals against an interior wall of left ventricle LV, thereby reducing paravalvular regurgitation across aortic valve AV and precluding proximal migration of anchor piece 550.

With anchor piece 550 deployed and native aortic valve AV displaced, valve piece 600 may be deployed and coupled to the anchor piece to achieve percutaneous aortic valve replacement. Outer tube 740 is further proximally retracted relative to inner tube 720 such that valve piece 600 is partially deployed from annular space 746 between inner tube 720 and outer tube 740, as seen in FIG. 45F. Expandable frame 620 coupled to replacement valve 610 partially self-expands such that tips 622 partially form hoop 624 for engagement of groove section 570 of anchor piece 550 (see FIG. 41B). A proximal end of expandable frame 620 is engaged by distal step 742 of outer tube 740.

Subsequent re-advancement of outer tube 740 relative to inner tube 720 causes distal step 742 to distally advance valve piece 600 within anchor piece 550 until tips 622 of expandable frame 620 engage groove section 570 of anchor piece 550, as seen in FIG. 45G. As discussed previously, groove section 570 comprises additional material and reduced openings or gaps G, as compared to previously known apparatus, which is expected to reduce native valve tissue protrusion through the gaps and facilitate engagement of tips 622 with the groove section. Outer tube 740 then is proximally retracted again relative to inner tube 720, and valve piece 600 is completely freed from annular space 746. Frame 620 of valve piece 600 fully expands to form hoop 624, as seen in FIG. 45H.

Hoop 624 friction locks within groove section 570 of anchor piece 550, thereby coupling the anchor piece to the valve piece and forming composite two-piece apparatus 510, which provides a percutaneous valve replacement. As seen in FIG. 451, delivery catheter 710 may then be removed from the patient, completing the procedure. Blood may freely flow from left ventricle LV through replacement valve 610 into aorta A. Coronary ostia O are unobstructed, and paravalvular regurgitation is reduced by skirt section 580 of anchor piece 550.

Referring now to FIGS. 46A-B, an alternative embodiment of two-piece apparatus 510 is described comprising an alignment/locking mechanism. Such a mechanism may be provided in order to ensure proper radial alignment of the expandable frame of the valve piece with the groove section of the anchor piece, as well as to ensure proper longitudinal positioning of the frame within the hoop. Additionally, the alignment/locking mechanism may provide a secondary lock to further reduce a risk of the anchor piece and the valve piece becoming separated post-deployment and coupling of the two pieces to achieve percutaneous valve replacement.

In FIGS. 46A-B, apparatus 510′ comprises valve piece 600′ of FIG. 46A and anchor piece 550′ of FIG. 46B. Anchor piece 550′ and valve piece 600′ are substantially the same as anchor piece 550 and valve piece 600 described hereinabove, except that anchor piece 550′ comprises first portion 652 of illustrative alignment/locking mechanism 650, while valve piece 600′ comprises second portion 654 of the alignment/locking mechanism for coupling to the first portion. First portion 652 illustratively comprises three guideposts 653 coupled to skirt section 580′ of anchor piece 550′ (only one guidepost shown in the partial view of FIG. 46B), while second portion 654 comprises three sleeves 655 coupled to posts 621 ′ of expandable frame 620′ of valve piece 600′.

When anchor piece 550′ is self-expanding and collapsed in the delivery configuration, guideposts 653 may be deployed with skirt section 580′, in which case guideposts 653 would rotate upward with respect to anchor piece 550′ into the deployed configuration of FIG. 46B. Alternatively, when anchor piece 550′ is either balloon or self-expanding and is collapsed in the delivery configuration, guideposts 653 may be collapsed against groove section 570′ of the anchor piece and may be deployed with the groove section. Deploying guideposts 653 with skirt section 580′ has the advantages of reduced delivery profile and ease of manufacturing, but has the disadvantage of significant dynamic motion during deployment. Conversely, deploying guideposts 653 with groove section 570′ has the advantage of minimal dynamic motion during deployment, but has the disadvantage of increased delivery profile. Additional deployment configurations will be apparent to those of skill in the art. As will also be apparent, first portion 652 of alignment/locking mechanism 650 may be coupled to alternative sections of anchor piece 550′ other than skirt section 580′.

Sleeves 655 of second portion 654 of alignment/locking mechanism 650 comprise lumens 656 sized for coaxial disposal of sleeves 655 about guideposts 653 of first portion 652. Upon deployment, sleeves 655 may friction lock to guideposts 653 to ensure proper radial and longitudinal alignment of anchor piece 550′ with valve piece 600′, as well as to provide a secondary lock of the anchor piece to the valve piece. The secondary lock enhances the primary friction lock formed by groove section 570′ of the anchor piece with hoop 624′ of expandable frame 620′ of the valve piece.

To facilitate coupling of the anchor piece to the valve piece, suture or thread may pass from optional eyelets 651 a of guideposts 653 through lumens 656 of sleeves 655 to a proximal end of the delivery catheter (see FIG. 47). In this manner, second portion 654 of mechanism 650 may be urged into alignment with first portion 652, and optional suture knots (not shown), e.g. pre-tied suture knots, may be advanced on top of the mechanism post-coupling of the two portions to lock the two portions together. Alternatively, guideposts 653 may comprise optional one-way valves 651 b to facilitate coupling of the first portion to the second portion. Specifically, sleeves 655 may be adapted for coaxial advancement over one-way valves 651 b in a first direction that couples the sleeves to guideposts 653, but not in a reverse direction that would uncouple the sleeves from the guideposts.

Referring now to FIG. 47, an alternative embodiment of apparatus 510′ comprising an alternative alignment/locking mechanism is described. Apparatus 510″ is illustratively shown in conjunction with delivery system 700 described hereinabove with respect to FIG. 42. Valve piece 600″ is shown partially deployed from outer tube 740 of catheter 710. For the sake of illustration, replacement valve 610″ of valve piece 600″, as well as inner tube 720 and middle distal tube 730 of delivery catheter 710, are not shown in FIG. 47.

In FIG. 47, anchor piece 550″ of apparatus 510″ comprises first portion 652′ of alignment/locking mechanism 650′, while valve piece 600″ comprises second portion 654′ of the alternative alignment/locking mechanism. First portion 652′ comprises eyelets 660 coupled to groove section 570″ of anchor piece 550″. Second portion 654′ comprises knotted loops of suture 662 coupled to tips 622″ of expandable frame 620″ of valve piece 600″. Suture 661 extends from knotted loops of suture 662 through eyelets 660 and out through annular space 746 between outer tube 740 and inner tube 720 (see FIG. 42) of catheter 710 to a proximal end of delivery system 700. In this manner, a medical practitioner may radially and longitudinally align valve piece 600″ with anchor piece 550″ by proximally retracting sutures 661 (as shown by arrows in FIG. 47) while distally advancing distal step 742 of outer tube 740 against valve piece 600″ until tips 622″ of the valve piece engage groove section 570″ of anchor piece 550″. Proximal retraction of outer tube 740 then causes expandable frame 620″ to further expand and form hoop 624″ that friction locks with groove section 570″ of anchor piece 550″, thereby forming apparatus 510″ as described hereinabove with respect to apparatus 510. A secondary lock may be achieved by advancing optional suture knots (not shown) to the overlap of eyelets 660 and knotted loops of suture 662. Such optional suture knots preferably are pre-tied.

With reference now to FIG. 48, yet another alternative embodiment of apparatus 510′, comprising yet another alternative alignment/locking mechanism 650, is described. First portion 652″ of alignment/locking mechanism 650″ is coupled to anchor piece 550′″ of apparatus 510′″, while second portion 654″ is coupled to valve piece 600′″. The first portion comprises male posts 670 having flared ends 671, while the second portion comprises female guides 672 coupled to tips 622′″ of expandable frame 620′″ of valve piece 600′″.

Female guides 672 are translatable about male posts 670, but are constrained by flared ends 671 of the male posts. In this manner, anchor piece 550′″ and valve piece 600′″ remain coupled and in radial alignment with one another at all times—including delivery—but may be longitudinally separated from one another during delivery. This facilitates percutaneous delivery without requiring a transseptal approach, while mitigating a risk of inadvertent deployment of the anchor and valve pieces in an uncoupled configuration. Additional alignment/locking mechanisms will be apparent in view of the mechanisms described with respect to FIGS. 46-48.

Prior to implantation of one of the replacement valves described above, it may be desirable to perform a valvoplasty on the diseased valve by inserting a balloon into the valve and expanding it using saline mixed with a contrast agent. In addition to preparing the valve site for implant, fluoroscopic viewing of the valvoplasty will help determine the appropriate size of replacement valve implant to use.

As discussed herein above, the location of the replacement heart valve, which may include, for example, anchor 30 and valve 20 shown in FIGS. 1A and 2A, may be assessed at any time during the deployment of the replacement heart valve. The replacement heart valve can be repositioned any number of time during deployment until it is in a desired location. The location of the replacement heart valve can generally be continuously assessed during the deployment procedure from delivery through final deployment and can be repositioned as necessary.

The anchor, such as the braid shown in FIGS. 17 and 18, can be at least partially deployed using exemplary delivery systems shown in FIGS. 5A-5F or FIGS. 49-53 by retracting a delivery sheath which allows the anchor to expand to a partially deployed configuration. The valve is preferably at least partially functional and more preferably is highly functional in this self-expanded state and therefore immediately begins to take on some of the function of the occluded and now non-functional native valve. Because the replacement heart valve is generally functional from its self expanded state through its fully deployed state, proper positioning can be incrementally attained with feedback provided continuously during the deployment process. A partially-deployed yet functional valve accommodates a wider range of feedback mechanisms in assessing the proper placement or location of the replacement heart valve prior to final, or full, deployment, and eventual release or resheathing of the heart valve. In addition, this functional valve also provides a larger temporal window within which to safely assess the location and reposition the replacement heart valve if necessary. The location of the replacement heart valve can therefore be assessed before the heart valve is fully deployed.

Assessing the location of the replacement heart valve can include visually observing the location of at least part of the replacement heart valve relative to at least one native anatomical landmark. Exemplary landmarks include, without limitation, the coronary ostia, the native leaflets, calcium nodules on the native valve within the leaflets or the aortic wall, the sinuses of valsalva, the native annulus, and the mitral valve.

Exemplary elements of the replacement heart valve that may be visually observed include, without limitation, the primary structure of the implant such as anchor 30 and valve 20 as shown in FIGS. 1A and 2A, the braid element such as anchor 30, the midline of braid 30 which can be further highlighted by a braid wire terminator. The proximal end of the replacement heart valve can be highlighted by the interface between, for example, the braid 350 and the tubes 352 shown in FIG. 24. Other coupler interfaces between the braid and delivery system may be used that can highlight the proximal end of the replacement heart valve. Proper foreshortening and proper braid locking in a fully deployed configuration can be visually observed by, for example, visualizing buckles 308 properly interfaced with posts 302 as shown in FIG. 18B.

Visually observing a position of the replacement heart valve relative to a native landmark to assess the location of the replacement heart valve include the following without limitation. The proximal end of the replacement heart valve is generally positioned below or at the level of the coronary ostia. The proximal end of the replacement heart valve may, however, be positioned above the level of the coronary ostia. As the ostia generally sit in a depression in the tissue wall, a replacement heart valve positioned above the level of the ostia would not necessarily block the openings to the ostia as a space would exist between the replacement heart valve and the ostia. In addition, blood generally flows into the ostia as backflow during diastole. The space between the replacement heart valve and the ostia could therefore allow the blood to flow back through the ostia even if the proximal end of the replacement heart valve were seated above the ostia. The mid-section of the replacement heart valve is generally in alignment with or near alignment with the native valve annulus. The distal end of the replacement heart valve is preferably positioned such that it does not reside in the space through which the mitral valve leaflets traverse as they function.

In addition to visually observing the position or location of the replacement heart valve, either relative to itself or to a native landmark(s), the shape of the anchor (e.g., braid) may be also be visually observed and assessed by visually observing the primary structure of the anchor. While a generally cylindrical shape is generally desirable, the anchor does not have to be completely cylindrical or even mostly cylindrical. For example, native features such as a calcified leaflet on one side of valve but not the other may affect the shape of the braid and yet the replacement heart valve may still function properly. Observing the shape of the anchor can include assessing the shape to ensure it is not in a shape that could negatively impact the proper functioning of the replacement heart valve.

Visually observing as described herein can include at least one medical imagine technique such as radiographic and ultrasonic techniques. Radiographic techniques as described herein includes without limitation x-ray, fluoroscopy (including angiograms), computed tomography (CT), magnetic resonance imaging (MRI), and methods reliant on scintalants or radioactive tracers. For example, 64 slice spiral CT or better resolution may be used, which either now exists or which may be developed in the future. Many of these techniques may additionally make use of contrast agents. Techniques measuring thermal diffusion flow may also be used. Ultrasound includes the use of intracardiac ultrasound (ICE).

Assessing the location of the replacement heart valve can be performed after the replacement heart valve has been expanded to the fully deployed configuration. Based on the assessment, the replacement heart valve can then be repositioned to a new location. Repositioning the heart valve can be done by distally pushing or proximally pulling on the anchor via a delivery system. The heart valve may also be collapsed before it is repositioned. The heart anchor may be, for example, collapsed to the self-expanded configuration, a partially re-sheathed/partially deployed configuration, or a fully re-sheathed configuration, depending on the configuration of the anchor prior to repositioning. The anchor and valve may then again be expanded and the location assessed using any of the techniques described herein. Once the replacement heart valve is in a desired position, the anchor is fully deployed, and may then be locked in the fully deployed expanded configuration.

Similar to assessing the location of the replacement valve, the operation, or performance, of the replacement valve can be assessed during the deployment process.

The replacement valve preferably begins to function as soon as it has emerged from the delivery catheter, even if the proximal end of the anchor remains inside the catheter. At this time, however, the valve may not be as efficient as when the valve is in a fully deployed configuration. Once the valve is fully deployed a final assessment on functionality is generally performed. Particularly, the valve leaflets preferably begin to function once they have been released from the catheter. FIGS. 49-53 illustrate the functionality of the valve in partially deployed configurations. FIG. 49 shows replacement heart valve 400, comprising a braid 401 and valve 402 as described herein, beginning to emerge from the delivery catheter 403. The valve 402 is disposed on the interior of the braid 401 as described herein and the valve 402 remains partially within the catheter. As such, the valve 402 is not yet functioning in FIG. 49. In FIG. 50, the valve 402 has fully emerged from the catheter 403 (and functional), while the proximal end of the braid remains in the catheter. This illustrates how the valve may be functional even if the braid is not fully deployed from the catheter. The flexibility of the braid allows for the distal end of the braid to greatly expand when it is released from the catheter even when the proximal end of the braid is still in the delivery catheter. This flexibility allows for the valve disposed at the distal end of the braid to function before the braid is completely released from the catheter. FIG. 51 shows a functional valve with length LV and the braid 401 emerging further from the catheter. FIGS. 52 and 53 illustrate a functioning valve with length LV and a braid 401 completely outside of the catheter with a length LB. FIG. 53 shows the length LB of braid 401 in the partially deployed, self-expanded configuration.

Because the replacement heart valve is preferably at least partially functional once the valve has completely emerged from the catheter, the operation, or functionality, of the replacement heart valve can be assessed from the time the valve is in this state until it is in the fully deployed configuration. The operation of the heart valve can also be assessed after the anchor is in the fully deployed configuration.

The functionality provided by the replacement valve once it emerges from the catheter is a distinct advantage over other percutaneously delivered valves. Such a valve accommodates the use of a wider range of feedback mechanisms in determining the proper placement of the implant prior to full deployment. In addition, such a valve also provides for a larger temporal window within which to safely ascertain and implement proper placement of the implant valve. Earlier generation percutaneously delivered valves such as balloon delivered valves, which do not begin to function until they are fully deployed and the balloon has been removed, do not benefit from these advantages. Such valves must be placed using only positional information to assure proper placement and such positional information must be attained in a very short period of time as the patient will be receiving no blood flow during this portion of the placement procedure. Additionally, even more recent generations of percutaneously delivered valves which are not reliant on balloon delivery may suffer from the same shortcoming. Such valves which exhibit a “biphasic” deployment, or where the valve snaps from a deployment configuration to a fully deployed configuration, will suffer from an inability to operate in an intermediate state and therefore do not accommodate the large range of functional feedback mechanisms to assess location and/or function, and the added time for acquisition and reflection on such information prior to their final deployment.

In preferred embodiments the operation of the valve can be assessed by visually observing the operation of the valve using any of the medical imaging techniques described herein or techniques known in the art, such as by performing an angiogram.

In some embodiments assessing the operation of the valve includes assessing the blood flow, such as by assessing blood velocity profiles, though or around the replacement heart valve. The blood flow can be observed during contraction to visualize blood flow through the valve. Valve leakage can be detected by observing blood flow around the valve, or by detecting regurgitation. Assessment also includes visually observing the valve to ensure sufficient effective orifice, sufficient ejection fraction, appropriate phase relationships between heart function and valve function, proper mitral valve function, and proper implant leaflet function. Assessment of the operation of the valve can help ensure, in addition to minimal valve leakage, proper replacement valve positioning and sizing. Thus, assessing the operation of the valve may be performed in conjunction with assessing the location of at least a portion of the replacement heart valve. For example, by assessing the operation of the valve and determining the valve is operating in a desired manner, the location of at least part of the braid may be deemed accurate.

One exemplary method of delivering a replacement heart valve and assessing the location and/or operation of the replacement heart valve is now described. More or fewer methods may, however, be performed.

A spiral CT scan is performed on the patient to generate a 3-dimensional image of the aortic valve to determine the size, or fit, of the replacement heart valve for the patient. The CT scan is currently performed using a stand-alone CT machine, however, a device capable of performing a CT scan as well as performing the imaging techniques described below is envisioned. An optional step to help determine the proper replacement heart valve size is to measure diameter changes of the annulus regions at various periods during the cardiac cycle in combination with pressure measurements to assess anatomical dimensions.

The patient is then taken to a separate room in which a pigtail is delivered to the site of the native valve to inject dye into the patients's vasculature. The same catheter is used to inject dye into the patient intermittently throughout the procedure to assess the location and function of the replacement heart valve as described herein.

A valvuloplasty is then performed by inserting a valvuloplasty device to open or “crack” the stenotic native valve, such as is described in pending U.S. application Ser. No. 11/314,969, filed Dec. 20, 2005. Performing the valvuloplasty can also assist in determining the correct size for the replacement heart valve. Alternatively, a balloon device which has a specific inflated outer diameter can be delivered to the site of the native valve and inflated. The native leaflets are forced against the aortic wall, “cracking” calcific materials embodied within the leaflets and aortic wall. This increases the effective orifice of the native valve and also can assist in determining the size of the valve to be deployed. Additionally, the “cracked” valve will be able to conform more easily to the perimeter of the replacement heart valve. The “creaked” native valve will also provide less resistance to the periphery of the subsequently delivered replacement valve during its deployment by decreasing the forces necessary to expand the replacement valve into a fully deployed configuration. The valvuloplasty balloon is then removed from the patient.

The valvuloplasty is followed by an angiogram using the imaging catheter. The angiogram allows visualization of the implant site and in particular the coronary ostia. The relation between calcific nodules and other native landmarks may also be visualized during this procedure. The eventual placement of the replacement heart valve is generally such that the ostia are not blocked by the replacement valve, thus avoiding a diminished blood supply to the heart. However, as described above, the replacement heart valve may be seated above the ostia without diminishing the blood supply into the ostia. As noted above, dye injections are done throughout the delivery and deployment procedure to continuously visually assess the location and/or function of the replacement heart valve.

After completing the preparation and initial visualization of the implant site, the distal end of the replacement valve is advanced in a retrograde fashion along the aorta to a location in apposition to the native valve. The delivery sheath is then retracted allowing the replacement heart valve to begin to self-expand. The valve preferably begins to function as soon as it completely emerges from the catheter, even when the proximal end of the braid remains in the catheter. Additional dye may be injected at this point to begin visually assessing the function of the valve.

After positioning the distal end of the delivery device in parallel with the native valve the outer sheath is removed, allowing the implant to expand to its self-expanded state. Angiographic means and/or ultrasonic means might then be used to more precisely visualize the position of the implant, thereby assuring that the self-expanded valve is properly distributed above and below the native annulus and functioning properly. The implant might then be foreshortened as described herein while continuously providing positional modifications, pushing the implant distally or pulling it proximally. In this manner, visually assessing the location and function can occur substantially continuously as the replacement valve is positioned and foreshortened to its fully deployed configuration. The implant might then be locked in its fully deployed configuration. At this time additional angiographic and ultrasonic images might be captured and used to verify that proper placement and proper and full functionality has been attained. A final CT scan may even be taken to verify full functionality. In the event that proper placement and or function have not been attained, the implant may be unlocked and readjusted into a more functionally appropriate position and relocked and again evaluated for proper performance. In the event that proper performance is not attainable and for any other appropriate reason the implant may be resheathed and completely removed at any point during the procedure. Upon resheathing the replacement valve, the native valve would once again assume its native functions.

While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby. 

What is claimed is:
 1. A method of assessing the operation of a replacement heart valve, the method comprising: endovascularly delivering a replacement heart valve to a vicinity of a heart valve in an unexpanded configuration; and assessing the operation of the replacement heart valve in the vicinity of the heart valve before fully expanding the replacement heart valve.
 2. The method of claim 1 wherein the replacement heart valve comprises a proximal end and a distal end, and wherein assessing the operation of the replacement heart valve comprises assessing the operation of the heart valve when the proximal end of the replacement heart valve is not engaging native tissue.
 3. The method of claim 2 wherein delivering comprises delivering the replacement heart valve within a delivery catheter, and wherein assessing the operation of the replacement heart valve comprises assessing the operation of the replacement heart valve while the proximal end of the replacement heart valve is disposed within the delivery sheath.
 4. The method of claim 1 wherein assessing the operation of the replacement heart valve comprises controlling blood flow through the replacement heart valve.
 5. The method of claim 1 wherein expanding the replacement heart valve to a fully expanded configuration comprises expanding the replacement heart valve to a partially deployed configuration.
 6. The method of claim 5 wherein expanding the replacement heart valve to a partially deployed configuration comprises allowing the replacement heart valve to self-expand to the partially deployed configuration.
 7. The method of claim 5 wherein assessing the operation of the replacement heart valve comprises controlling blood flow through the replacement heart valve.
 8. The method of claim 7 wherein assessing the operation of the replacement heart valve occurs after the replacement heart has self-expanded to the partially deployed configuration and before the replacement heart valve is expanded to the fully expanded configuration.
 9. The method of claim 1 wherein assessing the operation of the replacement heart valve comprises visually observing the operation of the replacement heart valve.
 10. The method of claim 9 wherein visually observing comprises visually observing with at least one medical imaging technique.
 11. The method of claim 10 wherein assessing the operation of the replacement heart valve comprises assessing the blood flow through or around the replacement heart valve.
 12. The method of claim 11 wherein assessing the blood flow through or around the replacement heart valve comprises assessing at least one of effective orifice, ejection fraction, and regurgitation.
 13. The method of claim 11 wherein assessing the blood flow through or around the replacement heart valve comprises assessing at least one of valve leakage, valve positioning, and valve sizing.
 14. The method of claim 10 wherein assessing the operation of the replacement heart valve comprises using an injectable marker.
 15. The method of claim 1 further comprising assessing the function of a mitral valve.
 16. The method of claim 1, further comprising reassessing the operation of the replacement heart valve after expanding the replacement heart valve to the fully expanded configuration.
 17. The method of claim 1, further comprising repositioning the replacement heart valve after assessing the operation of the replacement heart valve, and further comprising reassessing the operation of the replacement heart valve after repositioning the replacement heart valve.
 18. The method of claim 17 wherein repositioning the replacement heart valve comprises collapsing and re-expanding the replacement heart valve.
 19. The method of claim 1 further comprising assessing the location of the replacement heart valve in the vicinity of the heart valve before fully expanding the replacement heart valve.
 20. The method of claim 1 wherein assessing the operation of the replacement heart valve occurs before the replacement heart valve self-expands to an at-rest configuration. 